The present invention relates to a biochip for the determination of the concentration of one or more types of specific biomolecules in a sample and its fabrication, for example particularly, but not exclusively, a biochip and its fabrication.
Nowadays, fast and high throughput biomolecular based detection devices tend to be miniaturized and high-level of integration. A general term for such devices is called “biochip”. A biochip composes of a substrate for identifying the target from the sample solution being dispensed onto the substrate. Various sensing parts or the biomolecular reactants are facilitated on the substrate depending on specific applications. To enhance the in situ biochemical reaction efficiency, a close distance and locally high concentration of the reactant are both necessary. Therefore, efforts have been made to actively transport and replenish the target molecules, because these movements will increase opportunities for the target entities to meet/react with their counterparts, i.e. probe entities/biomolecules, which are normally immobilized on the substrate. Electrokinetics (EK) technologies have been developed and widely used as a mechanical-part-free, flexible and highly programmable tool for fluid and microparticle manipulation, especially in Lab-On-A-Chip (LOAC) platforms.
Currently, there are some limitations in EK manipulation in LOAC devices. Under DC electric field regime, electrophoresis (EP) technology has been widely applied, such as the well-known gel electrophoresis. In general, DC electric field is only effective for either positively or negatively charged entities at a time. For biomolecules having complex conformations and charge conditions, it is difficult to manipulate EP transportation with good consistency and efficiency. Besides, even the highly corrosion-resistant electrode, like Platinum (Pt), will degrade with the operation time, which would also affect the accuracy and efficiency of such devices. When using AC electric field, dielectrophoresis (DEP) have become an outstanding technology in manipulating any charged and neutral micro-particles. The major drawback of DEP is the short effective range, while other AC electrohydrodynamic (EHD) effects have been proven capable of driving fluids in longer range. However, the fluid flow is not efficient for confining and concentrating small molecules like nucleic acids.
Therefore, we seek to provide a comprehensive and robust solution to increase the efficiency of biochemical reaction through the conceptual design of device structures and fabrication method for combinational EK manipulations.